By taking advantage of the high activity of prostatic acid phosphatase (PAP) in prostatic epithelial cells and prostatic carcinoma cells in man and primates, we are designing agents that will become enzym-activated to cytotoxic agents specifically by PAP. This has been made possible by the discovery that PAP can hydrolyze phosphates containing basic nitrogen, whereas other acid phosphatases are unable to do so. This is indicated by the determination of the P/K ratio (hydrolysis by human prostate divided by that for human kidney). So far we have attacked the spindle poison, colchicine. We have prepared a number of derivatives that retain cytotoxicity and much less so afte they are phosphorylated. A high MTD ratio (Maximum Tolerated Dose) in mice of the phosphorylated agent divided by the MTD of the unphosphorylated agent, as well as a high P/K ratio will be sought before proceeding to evaluation against prostatic epithelial cells in dogs and primates.